X-ray imaging (radiography) is one of the most important and widely used medical diagnostic methods. It can be traced back to the invention of x-rays more than 100 years ago. Well-known applications include mammography, angiography, x-ray computerized tomography (CT) scans, and dental x-rays. For example, x-ray mammography is currently the primary method for breast cancer screening. Recent randomized clinical trials have shown that screening mammography has reduced mortality from breast cancer by 25 to 30 percent in women between the ages of 50 and 70 and by 18 percent among women between the ages of 40 and 50.
In addition to these essential medical applications, x-ray imaging is finding increasingly important applications in biomedical research laboratories, such as in the study of disease progression or effect of genetic engineering or drug therapy. Often, time-lapsed noninvasive, in vivo images of animal models are used. Often mouse models are used to study human disease. By coupling with genomics and molecular and cell biology, the study of the animal models using x-ray imaging will enable noninvasive investigations of biological processes in vivo and longitudinal studies in the same animal. Such studies can significantly contribute to the early detection, diagnosis, and treatment of disease, and to the understanding of disease progression and response to therapy that may contribute to the development of human medicine.
Continued performance improvements in x-ray imaging technology are essential for meeting the evolving needs in medical care and biomedical research. Important progress has been made in recent years in the following three areas: (1) use of source spectral properties that allow for the effective separation of images of soft tissue and hard or mineralized tissue; (2) increased acceptance and wide deployment of digital detectors that increase detection sensitivity and image dynamic range for imaging smaller features; and (3) use of phase contrast, instead of the absorption contrast that is predominately used in current x-ray imaging tools.
Phase contrast has been shown to provide substantial contrast enhancement for many applications and thus will result in a substantial reduction in the radiation dose to the subject. It is well established in recent years that contrast enhancement by more than several orders of magnitude can be achieved in imaging biological objects using phase contrast instead of the absorption contrast.
The phase contrast originates from phase shifting effect of x-rays between different features. The magnitude of the phase contrast is approximately proportional to mass density difference of the features. It has been well recognized that there is a need to develop a clinical-worthy x-ray imaging tool that employs phase contrast to achieve performance gains in terms of increasing detection sensitivity and spatial resolution and reduction of radiation dose to a patient.
Until now, typical phase-contrast imaging with a projection-type microscope requires two exposures with the detector placed at different distances from the sample. Motion-induced differences in the subject during the two exposures often cause artifacts in the reconstructed phase image and limit the image resolution to many tens of micrometers.
Significant progress has also been made in recent years in dual energy x-ray imaging systems. The dual energy x-ray imaging system produces extraordinary images of soft tissue as well as hard tissue, such as bones. Progress, however, is still needed to realize the full potential of this x-ray imaging for biomedical applications. For example, existing dual energy x-ray imaging tools require taking images at two substantially different x-ray spectra within a very short time (˜200 milliseconds) to reduce image blurring due to the movement of the object. The imaging tool uses a very specialized x-ray source for fast switching of the x-ray spectra and an expensive detector for extremely fast image readout because each single image contains large amounts of data.